Costa Silva V L, Campiglia S S, de Mello Aires M, Malnic G, Giebisch G
J Membr Biol. 1981;63(1-2):13-24. doi: 10.1007/BF01969441.
The acidification of kinetics of artificial solutions containing buffers of different permeancy were studied in rat proximal tubules by means of stationary microperfusion techniques. Luminal pH changes were measured by antimony microelectrodes and used to calculate net rates of acidification and the approach to steady-state pH levels. For most buffer species, tracer efflux out of the lumen was compared with changes in buffer concentration as derived from calculations based on the Henderson Hasselbalch equation. Steady-state luminal pH was similar for most buffer systems studied. However, secretory hydrogen ion fluxes into the lumen were significantly higher for permeant than for less permeant buffers. The most likely explanation is that permeant buffers behave as "open" systems maintaining constant low diffusible acid levels in the lumen, whereas impermeant buffers behave as "closed" systems in which non-ionized acid levels are maintained at higher levels. A behavior consistent with this thesis was directly demonstrated for glycodiazine and, to a lesser degree, for DMO. In contrast, phosphate and creatinine behave like buffers in a "closed" system. Characteristics of proximal tubular acidification, of buffer reabsorption, and the effect thereupon of carbonic anhydrase inhibitors are satisfactorily explained by an essential role of (1) hydrogen ion secretion, (2) pK differences, and (3) different permeance of the non-ionized buffer species. However, specific transport mechanisms may, in addition, also contribute to differences in transepithelial buffer movement.
采用固定微灌注技术,在大鼠近端小管中研究了含有不同通透性缓冲液的人工溶液的酸化动力学。通过锑微电极测量管腔pH变化,并用于计算酸化净速率和达到稳态pH水平的方法。对于大多数缓冲物质,将示踪剂从管腔中的流出与基于亨德森-哈塞尔巴尔赫方程计算得出的缓冲液浓度变化进行比较。所研究的大多数缓冲系统的稳态管腔pH相似。然而,可渗透缓冲液向管腔分泌的氢离子通量显著高于低渗透缓冲液。最可能的解释是,可渗透缓冲液表现为“开放”系统,维持管腔中恒定的低扩散酸水平,而不可渗透缓冲液表现为“封闭”系统,其中非离子化酸水平维持在较高水平。对于甘氨二嗪,在较小程度上对于二甲基异恶唑,直接证明了与该论点一致的行为。相比之下,磷酸盐和肌酐在“封闭”系统中表现得像缓冲液。近端小管酸化、缓冲液重吸收的特征以及碳酸酐酶抑制剂对其的影响,可以通过(1)氢离子分泌、(2)pK差异和(3)非离子化缓冲物质的不同通透性的重要作用得到满意的解释。然而,特定的转运机制此外也可能导致跨上皮缓冲液移动的差异。